Zhang Tao, Zhong Xin-Cao, Feng Zi-Xuan, Lin Xiao-Ying, Chen Chun-Ye, Wang Xiao-Wei, Guo Kai, Wang Yi, Chen Jun, Du Yong-Zhong, Zhuang Ze-Ming, Wang Yong, Tan Wei-Qiang
Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, China.
MOE Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Bioact Mater. 2024 Nov 27;45:322-344. doi: 10.1016/j.bioactmat.2024.11.028. eCollection 2025 Mar.
Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.
在临床环境中实现无瘢痕皮肤再生面临重大挑战。巨噬细胞表型转变失衡、上皮再形成延迟以及成纤维细胞过度增殖和分化等关键问题阻碍伤口愈合并导致纤维化修复。针对这些问题，我们开发了一种具有仿生机械功能的主动收缩和抗氧化水凝胶（P&G@LMs），以重塑愈合微环境并有效促进皮肤再生。水凝胶的即时止血作用引发了一系列重塑过程，其主动收缩特性在体温下封闭并收缩伤口，抗氧化功能消除活性氧，促进上皮再形成。炎症阶段LMs（血管紧张素转换酶抑制剂）的时空释放调节巨噬细胞向抗炎M2表型极化，促进向增殖阶段进展。然而，巨噬细胞的促纤维化微环境在肌成纤维细胞中诱导出高收缩性的α-平滑肌肌动蛋白阳性状态，而LMs的持续释放可以调节这种微环境以控制纤维化并促进胶原蛋白正确的生物力学取向。值得注意的是，水凝胶的仿生力学模仿了肌成纤维细胞的收缩特性，类似皮肤的弹性模量可以适应皮肤动态变化并恢复伤口缺损的机械完整性，部分替代肌成纤维细胞在组织修复中的机械作用。本研究提出了一种创新的皮肤再生策略。
